Abstract

The effects of infusing the glutamate receptor agonist α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) on the release of dopamine (DA) has been studied in rat hippocampus and striatum in vivo. In hippocampus, AMPA (1–10 μM) produced a dose related increase in dialysate DA, but at 100 μM AMPA a sustained decrease in extracellular DA was observed. However, when samples were collected at 5-min intervals 100 μM AMPA infusion revealed a brief increase in hippocampal dialysate DA. Infusion of 100 μM AMPA and 100 μM diazoxide, which blocks AMPA receptor desensitization, led to a marked increase in extracellular DA, as did diazoxide alone, although to a lesser extent. The AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3,-dione (CNQX; 200 μM) reversed the effect of AMPA and/or diazoxide infusion on dialysate DA and when infused alone, CNQX also decreased hippocampal dialysate DA. AMPA (50–500 μM) increased striatal DA release. The effect of AMPA on extracellular DA was reversed by CNQX (200 μM). Diazoxide infusion caused a decrease in striatal DA release, and this was not affected by CNQX. These data suggest that hippocampal, but not striatal AMPA receptor desensitization may play a role in regulating DA release.